Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition
Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell.
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Author
Krammer, Teresa;
Stuart, Hannah T.;
Gromberg, Elena;
Ishihara, Keisuke;
Cislo, Dillon;
Melchionda, Manuela;
Becerril Perez, Fernando;
Wang, Jingkui;
Costantini, Elena;
Rus, StefanieISTA 
;
Arbanas, Laura;
Hörmann, Alexandra
All
;
Arbanas, Laura;
Hörmann, Alexandra
All
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Abstract
During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable “winning” floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.
Publishing Year
Date Published
2024-05-21
Journal Title
Developmental Cell
Publisher
Elsevier
Acknowledgement
We thank P. Pasierbek, A.C. Moreno, T. Lendl, and K. Aumayr for microscopy support; G. Schmauss for FACS support; M. Novatchkova for assistance with Bioinformatic analyses; J. Ahel, A. Polikarpova, S. Horer, E. Cesare, and E. Norouzi for technical assistance; A. Meinhardt for supervision; DRESDEN-concept Genome Center, A. Vogt, A. Sommer, and the Vienna BioCenter NGS facility for RNA sequencing. We are grateful to M. Placzek and E. Martí for discussions about the floorplate; to S. Shvartsman for valuable input; to A. Aszodi, W. Masselink, and S. Raiders for advice on statistical analyses; to J. Cornwall Scoones, G. Martello, and Tanaka lab members for critical reading of the manuscript; E. Bassat and E. Chatzidaki for contributing schematics; and to K. Lust for support. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement ERC AdG 742046) to E.M.T. This research was funded in whole or in part by the Austrian Science Fund (FWF) (10.55776/F7803-B) (Stem Cell Modulation) to E.M.T. and A.K., Sir Henry Wellcome postdoctoral fellowship to H.T.S., ELBE fellowship to K.I., and National Science Foundation (US) Phy 2013131 to E.S. The A.K. lab is also supported by ISTA and the European Research Council under Horizon Europe grant 101044579, and S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. This work was supported in part by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome Trust (CC001051). For the purpose of open access, the authors have applied a CC BY public copyright license to any author accepted manuscript (AAM) version arising from this submission.
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Cite this
Krammer T, Stuart HT, Gromberg E, et al. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. doi:10.1016/j.devcel.2024.04.021
Krammer, T., Stuart, H. T., Gromberg, E., Ishihara, K., Cislo, D., Melchionda, M., … Tanaka, E. M. (n.d.). Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2024.04.021
Krammer, Teresa, Hannah T. Stuart, Elena Gromberg, Keisuke Ishihara, Dillon Cislo, Manuela Melchionda, Fernando Becerril Perez, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” Developmental Cell. Elsevier, n.d. https://doi.org/10.1016/j.devcel.2024.04.021.
T. Krammer et al., “Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition,” Developmental Cell. Elsevier.
Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell.
Krammer, Teresa, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” Developmental Cell, Elsevier, doi:10.1016/j.devcel.2024.04.021.
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